Preparation And Application Of Ultrasmall-Sized Nano-Contrast Agents

Medical imaging has been employed as a visual diagnostic platform in clinical and scientific research.Especially,magnetic resonance imaging（MRI）with non-invasive,high soft-tissue contrast,and high spatial resolution and computed tomography（CT）with high hard-tissue contrast,high spatial and density resolution have been widely used for the diagnosis of clinical diseases.For enhancing the sensitivity of CT and MRI imaging,iodine compounds are used as CT contrast agents and Gd chelates are used as positive T1 contrast agents for MRI clinically.However,they have shortcomings such as single imaging mode,difficult modification,short imaging time and low sensitivity.Owing to the inherent advantages and disadvantages of each imaging mode,any single imaging mode does not provide complete diagnosis of complex diseases.So,it is very necessary to develop CT/MRI multifunctional contrast agents.Compared with single-mode CT or MRI contrast agents,multifunctional CT/MRI contrast agents can improve imaging accuracy,speed up imaging,and avoid the damage and side effects caused by multiple injections.With the development of nanotechnology,there is an immense increase of nanoparticles considered as promising diagnostic agents due to their excellent optical,electrical and magnetic properties in the field of nanomedicine.Especially,ultrasmall-sized nanoparticles have been employed as CT/T1-MRI multifunctional contrast agents.Ultrasmall-sized nano-contrast agents can improve the sensitivity of the contrast agents due to their large specific surface areas/volume ratios,reducing the dose and the side reactions,but also avoid the capture of the endothelial network,increasing the circulation in the blood.Simultaneousluy,they can be excreted through the kidneys after prolonged imaging,reducing potential biotoxicity.Ultrasmall-sized Bi₂S₃ nanoparticles are used as CT contrast agents because of their large X-ray attenuation coefficient.Additionaly,MPt（M=Fe、Co or Ni）alloys as biocompatible magnetic nanomaterials provide excellent platforms for constructing CT/T1-MRI multifunctional contrast agents.Based on the above backgrounds,this thesis studied the ultrasmall-sized Bi₂S₃ CT contrast agents and the preparation and application of ultrasmall-sized MPt CT/T1-MRI multifunctional contrast agents.The main work includes the following three aspects:（1）An economical synthesis strategy was developed for the large-scale preparation of ultrasmall-sized Bi₂S₃ nanoparticles.Then,the cytotoxicity,in vitro and vivo CT imaging effects were further explored.The as-prepared ultrasmall-sized Bi₂S₃ CT contast agents possessed excellent CT imaging performances that were employed for long-term and highly sensitive CT imaging.It was worth notice that they could be excreted through the bladder after long-term CT imaging.The results indicate that they owned low cytotoxicity and excellent CT imaging performances.This work laid good foundations for constructions of CT/T1-MRI multi-functional contrast agent platform.（2）The ultrasmall-sized MPt nanoparticles were prepared and modified with PEG.Then,the CT/T1-MRI dual-mode imaging performances were explored in vitro and vivo.Three ultrasmall-sized nano-contrast agents had high sensitivity of CT and T1-MRI imaging compared with iodixanol and guanidine diamine.The results suggest that they not only possessed high sensitivity for CT/T1-MRI dual-modal imaging.Simultaneously,the doses can be reduced,reducing the side reactions due to high sensitivity.Additionaly,they could be well metabolized through the bladder after long-term imaging,reducing the potential bio-toxicity of the organism.This chapter successfully constructed three high-performance CT/T1-MRI multifunctional nano-contrast agents with ultrasmall-sized MPt,which provides visual platforms for the efficient diagnosis of diseases.（3）The cytotoxicity,tissue and in vivo toxicity of ultrasmall-sized MPt contrast agents were explored.The results show that they have excellent biocompatibility.The work lays good foundations for further biological application and clinical transformation,and also promotes the development of ultrasmall-sized multifunctional nano-contrast agents.